背景:先天性角化病1(DKC1),端粒酶复合物的关键成分,在多种人类癌症中高表达。然而,DKC1与癌症发生和发展阶段的关系尚不清楚,使泛癌症分析至关重要。
方法:我们使用各种生物信息学数据库进行了一项研究,例如TIMER,GEPIA,UALCAN,和KM绘图仪分析,以检查DKC1在多个组织中的不同表达及其与病理分期的相关性。通过KEGG分析,GO富集分析和Venn分析,我们能够揭示DKC1相关基因和信号通路。此外,我们进行了几个测试,包括CCK,伤口愈合试验,细胞周期停滞试验,对DKC1缺失的MDA-231细胞进行transwell分析和Sa-β-gal染色。
结果:我们的研究表明,DKC1在不同组织中的表达特异性相对较低。此外,我们发现在ACC中,KICH,KIRP和LIHC,DKC1的表达水平与病理分期呈正相关。相反,在NHSC,KIRP,LGG,LIHC,MESO和SARC,我们观察到DKC1表达水平对总生存率有负面影响。我们还发现在14种肿瘤中DKC1表达与肿瘤突变负担之间存在显著正相关。此外,我们观察到DKC1DNA甲基化对BRCA启动子区基因表达的显著负面影响.我们还鉴定了许多集中在DKC1蛋白C末端的磷酸化位点。我们的GO分析揭示了DKC1和核糖体生物合成途径之间的相关性,并确定了共同元素UTP14A。我们还观察到细胞增殖率下降,DKC1敲除MDA-MB-231细胞系的迁移和侵袭能力。此外,DKC1敲除诱导细胞周期停滞并引起细胞衰老。
结论:我们的发现表明,DKC1的精确表达与多种组织中癌症的发生和发展阶段密切相关。DKC1的耗竭可以抑制癌细胞的增殖能力,migrate,并通过阻止细胞周期和诱导细胞衰老来入侵。因此,DKC1可能是诊断和治疗各种组织中癌症的有价值的预后生物标志物。
BACKGROUND: Dyskeratosis congenita 1 (DKC1), a critical component of telomerase complex, is highly expressed in a variety of human cancers. However, the association of DKC1 with cancer occurrence and development stages is not clear, making a pan-cancer analysis crucial.
METHODS: We conducted a study using various bioinformatic databases such as TIMER, GEPIA, UALCAN, and KM plotter Analysis to examine the different expressions of DKC1 in multiple tissues and its correlation with pathological stages. Through KEGG analysis, GO enrichment analysis and Venn analysis, we were able to reveal DKC1-associated genes and signaling pathways. In addition, we performed several tests including the CCK, wound healing assay, cell cycle arrest assay, transwell assay and Sa-β-gal staining on DKC1-deleted MDA-231 cells.
RESULTS: Our study demonstrates that DKC1 has relatively low expression specificity in different tissues. Furthermore, we found that in ACC, KICH, KIRP and LIHC, the expression level of DKC1 is positively correlated with pathological stages. Conversely, in NHSC, KIRP, LGG, LIHC, MESO and SARC, we observed a negative influence of DKC1 expression level on the overall survival rate. We also found a significant positive correlation between DKC1 expression and Tumor Mutational Burden in 14 tumors. Additionally, we observed a significantly negative impact of DKC1 DNA methylation on gene expression at the promoter region in BRCA. We also identified numerous phosphorylation sites concentrated at the C-terminus of the DKC1 protein. Our GO analysis revealed a correlation between DKC1 and ribosomal biosynthesis pathways, and the common element UTP14A was identified. We also observed decreased rates of cell proliferation, migration and invasion abilities in DKC1-knockout MDA-MB-231 cell lines. Furthermore, DKC1-knockout induced cell cycle arrest and caused cell senescence.
CONCLUSIONS: Our findings suggest that the precise expression of DKC1 is closely associated with the occurrence and developmental stages of cancer in multiple tissues. Depletion of DKC1 can inhibit the abilities of cancer cells to proliferate, migrate, and invade by arresting the cell cycle and inducing cell senescence. Therefore, DKC1 may be a valuable prognostic biomarker for the diagnosis and treatment of cancer in various tissues.